Neuropsychological testing has revealed that affectively ill patients have impaired performance on the Halstead Category Test and recognition of facial emotional expression, in contrast with unimpaired verbal emotion recognition tasks. The impairment in facial emotion recognition is state-related; i.e., more profound during expression than the "well- interval" between episodes. Patients also report lifetime disturbances in tasks and activities of daily living including visual spatial processing, but not those in the verbal mode. The neural substrates of these deficits are being systematically explored by a variety of techniques including testing patients utilizing 015 blood flow studies with PET methodology (see MH 02636-02 BPB and MH 02638-02 BPB). Earlier CAT scan studies have revealed increased VBR in patients with affective disorders unrelated to the course of illness, but positively related to age, measures of cortisol hypersecretion, and impairment on the Halstead Category Test. More recent MRI studies suggest decreased area and volume of the temporal lobe in affectively ill subjects compared with controls. Periventricular abnormalities have been observed in BP-I patients on T2 weighted scans; these findings are of interest in relation to increased CSF protein in bipolar-I patients as well. Evidence of frontal hypometabolism is revealed on PET scan studies in patients with primary affective disorders as well as depression associated with epilepsy. This correlated with severity of depression rated on the Hamilton Depression Scale. Temporal and parietal alterations are also evident. Frontal hypometabolism predicts response to nimodipine (and bupropion or venlafaxine in outpatients), hyperactivity, particularly in temporal lobes, is associated with response to carbamazepine. We wish to see whether neuropsychological profiles can also predict response to lithium and these agents. Affectively ill patients like these with epilepsy have a high incidence of paroxysmal psychosensory symptoms during their episodes; preliminary evidence suggests that this is unrelated to acute antidepressant or antimanic response to carbamazepine, and is paradoxically associated with a poorer response to carbamazepine in long- term prophylaxis.